The ability of malignant gliomas to disperse within normal brain ultimately renders ineffective all of our current therapies for this tumor. This invasive propensity is further stimulated by antiangiogenics, which have entered the mainstream of glioma therapeutics. Unfortunately, treatments designed to block this invasive phenotype do not produce universal or durable response, which underscores the need to find new ways of targeting brain dispersion by this tumor. In our prior work, we established that the molecular motor non-muscle myosin II (NMMII) is an essential component of the glioma invasion apparatus. In this application, we will examine the roles of NMMII in driving glioma invasion and the efficacy of targeting NMMII in blocking the invasive phenotype of malignant gliomas in a set of realistic and robust preclinical models of glioblastoma. Results from these translational studies will be combined with combination therapy studies in our pre-clinical models in order to identify potential synergy between NMMII inhibitors and anti-angiogenic and radiation therapy.